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Low-Dose TBI and Fludarabine Followed by Unrelated Donor Stem Cell Transplantation for Patients With Hematologic Malignancies and Renal Cell Carcinoma - A Multi-Center Trial.


N/A
N/A
N/A
Open (Enrolling)
Both
Accelerated Phase Chronic Myelogenous Leukemia, Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), B-cell Chronic Lymphocytic Leukemia, Childhood Acute Lymphoblastic Leukemia in Remission, Childhood Acute Myeloid Leukemia in Remission, Childhood Chronic Myelogenous Leukemia, Childhood Myelodysplastic Syndromes, Childhood Renal Cell Carcinoma, Chronic Phase Chronic Myelogenous Leukemia, Clear Cell Renal Cell Carcinoma, de Novo Myelodysplastic Syndromes, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Nodal Marginal Zone B-cell Lymphoma, Previously Treated Myelodysplastic Syndromes, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Hodgkin Lymphoma, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Small Lymphocytic Lymphoma, Recurrent/Refractory Childhood Hodgkin Lymphoma, Refractory Chronic Lymphocytic Leukemia, Refractory Hairy Cell Leukemia, Refractory Multiple Myeloma, Relapsing Chronic Myelogenous Leukemia, Splenic Marginal Zone Lymphoma, Stage IV Renal Cell Cancer, T-cell Large Granular Lymphocyte Leukemia, Type 1 Papillary Renal Cell Carcinoma, Type 2 Papillary Renal Cell Carcinoma, Waldenström Macroglobulinemia

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Trial Information

Low-Dose TBI and Fludarabine Followed by Unrelated Donor Stem Cell Transplantation for Patients With Hematologic Malignancies and Renal Cell Carcinoma - A Multi-Center Trial.


PRIMARY OBJECTIVES:

I. To determine whether stable allogeneic engraftment from unrelated hematopoietic stem cell
donors can be safely established using a non-myeloablative conditioning regimen in patients
with hematologic malignancies and renal cell carcinoma.

SECONDARY OBJECTIVES:

I. To evaluate whether donor lymphocyte infusion (DLI) can be safely used in patients with
mixed or full donor chimerism to eliminate persistent or progressive disease.

OUTLINE:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4
to -2. Patients also undergo low-dose total-body irradiation (TBI) on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) or bone
marrow transplantation on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to
100 with taper to day 177 and mycophenolate mofetil PO BID on days 0-40 with taper to day
96. Patients with mixed chimerism, persistent or progressive disease, and no evidence of
graft-versus-host disease and who have been off immunosuppression for at least 2 weeks
undergo DLI over 30 minutes. DLI may be repeated every 65 days for up to 3 doses.

After completion of study treatment, patients are follow-up periodically for 5 years.


Inclusion Criteria:



- Age > 50 years with hematologic malignancies treatable by allogeneic hematopoietic
stem cell transplant (HSCT) and all patients with B cell malignancies except those
who may be cured by autologous stem cell transplantation (SCT)

- Age =< 50 years of age with hematologic diseases treatable by allogeneic HSCT who
through pre-existing medical conditions or prior therapy are considered to be of high
risk for regimen related toxicity associated with a conventional transplant or those
patients who refuse a conventional SCT; transplants must be approved for these
inclusion criteria by both the participating institution's patient review committee
such as the Patient Care Conference (PCC at the Fred Hutchinson Cancer Research
Center [FHCRC]) and by the principal investigator

- Patients with metastatic renal cell carcinoma with the histologic subtypes of clear
cell, papillary and medullary may be accepted regardless of age

- The following diseases will be permitted although other diagnoses can be considered
if approved by PCC or the participating institution's patient review committees and
the principal investigator

- Non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), Hodgkin lymphoma
(HL) - must have received and failed frontline therapy

- Multiple myeloma - must have received prior chemotherapy; consolidation of
chemotherapy by autografting prior to nonmyeloablative HSCT is permitted

- Acute myeloid leukemia (AML)/acute lymphoblastic leukemia (ALL) - must be in
complete remission and have received cytotoxic chemotherapy at some stage before
transplant; patients with molecular or early relapse will be accepted providing
a donor is available; patients with persistent or refractory disease will be
considered on a case by case basis and transplants must be approved by the
institution's patient review committees

- Chronic myelogenous leukemia (CML) - Patients will be accepted in chronic phase
or accelerated phase; patients who have received prior autografts after high
dose therapy or have undergone intensive chemotherapy for either peripheral
blood stem cell (PBSC) mobilization or treatment of advanced CML may be enrolled
provided they are in complete remission (CR), chronic phase (CP) or accelerated
phase (AP)

- Myelodysplastic syndromes (MDS) - All patients with MDS will be eligible for
this protocol; however, those patients with MDS and frank AML (>30% blasts in
bone marrow aspirate by morphology or flow cytometry) will require induction
chemotherapy to obtain a complete remission (marrow blasts < 5%) and remain in
complete remission at time of transplant

- Renal Cell Carcinoma- Must have evidence of disease not amenable to surgical
cure or metastatic disease by radiological and histological criteria

- DONOR: Human leukocyte antigen (HLA) matched unrelated donor; donors should be
matched for HLA -A, -B, -C, -developmentally regulated RNA binding protein 1(DRB)1
and -class II, DQ beta 1(DQB)1; HLA -A and -B loci should be matched at least to the
level of resolution specified in Appendix I; HLA -C, -DRB1, and -DQB1 should be typed
at the highest level of resolution available at the time of donor selection; donor
must consent to either a bone marrow harvest or PBSC mobilization with filgrastim
(G-CSF) arranged through the National Marrow Donor Program (NMDP) or other donor
centers

Exclusion Criteria:

- Patients with rapidly progressive intermediate or high grade NHL

- Renal Cell Carcinoma patients with expected survival of less than 6 months

- Bulky disease resulting in severely limited performance status (< 70%)

- Any vertebral instability

- Any active central nervous system (CNS) involvement with disease

- Fertile men or women unwilling to use contraceptive techniques during and for 12
months following treatment

- Females who are pregnant

- Patients with non-hematological tumors

- Cardiac ejection fraction < 30%

- Pulmonary: Diffusion capacity of carbon monoxide (DLCO) < 30% and/or receiving
supplementary continuous oxygen

- Liver function abnormalities: Significant elevation of bilirubin and transaminases
should be discussed at participating institutions' patient review committees in a
case by case basis; evidence of synthetic dysfunction or severe cirrhosis will result
in patient exclusion

- Karnofsky score < 50 (except renal cell carcinoma [RCC])

- Patients with poorly controlled hypertension on multiple antihypertensives

- Human immunodeficiency virus (HIV) positive patients

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Establishment of an allograft as defined by stable mixed chimerism or full donor chimerism

Outcome Description:

Engraftment will be assessed separately among patients who receive bone marrow and patients who receive PBSC. Patients with low-risk and high-risk disease will be assessed separately.

Outcome Time Frame:

At day 56

Safety Issue:

No

Principal Investigator

Brenda Sandmaier

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Federal Government

Study ID:

1463.00

NCT ID:

NCT00005799

Start Date:

November 1999

Completion Date:

Related Keywords:

  • Accelerated Phase Chronic Myelogenous Leukemia
  • Adult Acute Lymphoblastic Leukemia in Remission
  • Adult Acute Myeloid Leukemia in Remission
  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
  • Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
  • B-cell Chronic Lymphocytic Leukemia
  • Childhood Acute Lymphoblastic Leukemia in Remission
  • Childhood Acute Myeloid Leukemia in Remission
  • Childhood Chronic Myelogenous Leukemia
  • Childhood Myelodysplastic Syndromes
  • Childhood Renal Cell Carcinoma
  • Chronic Phase Chronic Myelogenous Leukemia
  • Clear Cell Renal Cell Carcinoma
  • de Novo Myelodysplastic Syndromes
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Nodal Marginal Zone B-cell Lymphoma
  • Previously Treated Myelodysplastic Syndromes
  • Recurrent Adult Acute Lymphoblastic Leukemia
  • Recurrent Adult Acute Myeloid Leukemia
  • Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
  • Recurrent Adult Hodgkin Lymphoma
  • Recurrent Childhood Acute Lymphoblastic Leukemia
  • Recurrent Childhood Acute Myeloid Leukemia
  • Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Recurrent Mycosis Fungoides/Sezary Syndrome
  • Recurrent Small Lymphocytic Lymphoma
  • Recurrent/Refractory Childhood Hodgkin Lymphoma
  • Refractory Chronic Lymphocytic Leukemia
  • Refractory Hairy Cell Leukemia
  • Refractory Multiple Myeloma
  • Relapsing Chronic Myelogenous Leukemia
  • Splenic Marginal Zone Lymphoma
  • Stage IV Renal Cell Cancer
  • T-cell Large Granular Lymphocyte Leukemia
  • Type 1 Papillary Renal Cell Carcinoma
  • Type 2 Papillary Renal Cell Carcinoma
  • Waldenström Macroglobulinemia
  • Congenital Abnormalities
  • Carcinoma
  • Carcinoma, Renal Cell
  • Hodgkin Disease
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Hairy Cell
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myeloid, Accelerated Phase
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myeloid, Chronic-Phase
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Non-Hodgkin
  • Waldenstrom Macroglobulinemia
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Mycoses
  • Mycosis Fungoides
  • Myelodysplastic Syndromes
  • Preleukemia
  • Sezary Syndrome
  • Lymphoma, B-Cell
  • Lymphoma, T-Cell
  • Lymphoma, T-Cell, Cutaneous
  • Lymphoma, B-Cell, Marginal Zone
  • Hematologic Neoplasms
  • Leukemia, Large Granular Lymphocytic

Name

Location

Stanford UniversityStanford, California  94305
Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109
University of ColoradoDenver, Colorado  80217
Baylor University Medical CenterDallas, Texas  75246
City of Hope Medical CenterDuarte, California  91010
University of UtahSalt Lake City, Utah